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Lactate AND Metformin

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https://www.readbyqxmd.com/read/28513118/metformin-does-not-induce-hyperlactatemia-in-patients-admitted-to-internal-medicine-ward
#1
Shlomit Koren, Shani Zilberman-Itskovich, Ronit Koren, Keren Doenyas-Barak, Ahuva Golik
BACKGROUND: Concerns about metformin-associated lactic acidosis (MALA) prohibit the use of metformin in a large subset of diabetic patients, mostly in patients with chronic kidney disease. Increasing evidence suggests that the current safety regulations may be overly restrictive. OBJECTIVES: To examine the association between chronic metformin treatment and lactate level in acute illness on the first day of admission to an internal medicine ward. METHODS: We compared diabetic and non-diabetic hospitalized patients treated or not treated with metformin in different sets of kidney function...
May 2017: Israel Medical Association Journal: IMAJ
https://www.readbyqxmd.com/read/28499942/metformin-ameliorates-hypoxia-reoxygenation-induced-cardiomyocyte-apoptosis-based-on-the-sirt3-signaling-pathway
#2
Yanyan Du, Jingjing Zhang, Fang Fang, Xiqing Wei, Hongsheng Zhang, Hongyong Tan, Jinguo Zhang
Myocardial hypoxia/reoxygenation (H/R) injury is one of the main causes of death and disability worldwide. However, a limited number of therapies are available to minimize the detrimental effects of this injury. Recently, researchers have demonstrated that metformin exerts direct cardioprotective effects against H/R. The aim of this study was to investigate the underlying mechanisms of how metformin affects myocardial hypoxia/reoxygenation (H/R) injury. In our study, the activities of lactate dehydrogenase (LDH) and superoxide dismutase (SOD) as well as the levels of malondialdehyde (MDA) were measured...
May 9, 2017: Gene
https://www.readbyqxmd.com/read/28497164/metformin-prevents-ischaemic-ventricular-fibrillation-in-metabolically-normal-pigs
#3
Li Lu, Shuyu Ye, Rebecca L Scalzo, Jane E B Reusch, Clifford R Greyson, Gregory G Schwartz
AIMS/HYPOTHESIS: Metformin is the drug most often used to treat type 2 diabetes. Evidence suggests that metformin may reduce mortality of individuals with type 2 diabetes, but the mechanism of such an effect is unknown and outcomes of metformin treatment in people without diabetes have not been determined. If metformin favourably affected mortality of non-diabetic individuals, it might have even broader therapeutic utility. We evaluated the effect of metformin on myocardial energetics and ischaemic ventricular fibrillation (VF) in metabolically normal pigs...
May 11, 2017: Diabetologia
https://www.readbyqxmd.com/read/28474741/metformin-and-daclatasvir-absence-of-a-pharmacokinetic-pharmacodynamic-drug-interaction-in-healthy-volunteers
#4
Elise J Smolders, Angela Colbers, Clara T M M de Kanter, Kirsten Velthoven-Graafland, Leonie T Wolberink, Noor van Ewijk-Beneken Kolmer, Joost P H Drenth, Rob E Aarnoutse, Cees J Tack, David M Burger
AIM: The aim of this study was to evaluate the effect of the proposed organic cation transporter (OCT) inhibitor daclatasvir on the pharmacokinetics and pharmacodynamics of the OCT substrate metformin. METHODS: This was an open-label, two-period, randomized, crossover trial in 20 healthy subjects. Treatment A consisted of metformin and treatment B consisted of metformin + daclatasvir. Pharmacokinetic curves were recorded at steady state. Geometric mean ratios (GMRs) with 90% confidence intervals (CIs) were calculated for metformin area under the concentration-time curve from 0 to 12 hours (AUC0-12 ), maximum plasma concentration (Cmax ) and final plasma concentration (Clast )...
May 5, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28432751/acute-kidney-injury-plasma-lactate-concentrations-and-lactic-acidosis-in-metformin-users-a-godarts-study
#5
Paul J Connelly, Mike Lonergan, Enrique Soto-Pedre, Louise Donnelly, Kaixin Zhou, Ewan R Pearson
AIMS: Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. METHODS: We undertook a population-based case-control study of lactic acidosis in 1,746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994-2014...
April 21, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28393220/metformin-increases-sensitivity-of-osteosarcoma-stem-cells-to-cisplatin-by-inhibiting-expression-of-pkm2
#6
Depeng Shang, Ju Wu, Lianyi Guo, Yanju Xu, Lezi Liu, Jianmin Lu
Multiple drug resistance is reported to be a major obstacle in treatment of osteosarcoma (OS). Research has demonstrated that small subsets of cells called cancer stem cells (CSCs) are responsible for multiple drug resistance. CSCs are potential targets for reversing chemoresistance. In the present study, we compared cisplatin sensitivity between OS stem cells and OS non-stem cells. We confirmed that OS stem cells showed significant cisplatin-resistance compared with the OS non-CSCs. Mechanically, we proved that overexpression of the pyruvate kinase isoenzyme M2 (PKM2) was responsible for the resistance to cisplatin in OS stem cells...
May 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28316081/the-antidiabetic-drug-metformin-decreases-mitochondrial-respiration-and-tricarboxylic-acid-cycle-activity-in-cultured-primary-rat-astrocytes
#7
Michaela C Hohnholt, Eva-Maria Blumrich, Helle S Waagepetersen, Ralf Dringen
Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping (13) C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-(13) C]glucose...
March 19, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28230778/caffeic-acid-expands-anti-tumor-effect-of-metformin-in-human-metastatic-cervical-carcinoma-htb-34-cells-implications-of-ampk-activation-and-impairment-of-fatty-acids-de-novo-biosynthesis
#8
Malgorzata Tyszka-Czochara, Pawel Konieczny, Marcin Majka
The efficacy of cancer treatments is often limited and associated with substantial toxicity. Appropriate combination of drug targeting specific mechanisms may regulate metabolism of tumor cells to reduce cancer cell growth and to improve survival. Therefore, we investigated the effects of anti-diabetic drug Metformin (Met) and a natural compound caffeic acid (trans-3,4-dihydroxycinnamic acid, CA) alone and in combination to treat an aggressive metastatic human cervical HTB-34 (ATCC CRL-1550) cancer cell line...
February 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28222147/the-desert-gerbil-psammomys-obesus-as-a-model-for-metformin-sensitive-nutritional-type-2-diabetes-to-protect-hepatocellular-metabolic-damage-impact-of-mitochondrial-redox-state
#9
Inès Gouaref, Dominique Detaille, Nicolas Wiernsperger, Naim Akhtar Khan, Xavier Leverve, Elhadj-Ahmed Koceir
INTRODUCTION: While metformin (MET) is the most widely prescribed antidiabetic drug worldwide, its beneficial effects in Psammomys obesus (P. obesus), a rodent model that mimics most of the metabolic features of human diabetes, have not been explored thoroughly. Here, we sought to investigate whether MET might improve insulin sensitivity, glucose homeostasis, lipid profile as well as cellular redox and energy balance in P. obesus maintained on a high energy diet (HED). MATERIALS AND METHODS: P...
2017: PloS One
https://www.readbyqxmd.com/read/28188168/metformin-associated-lactic-acidosis-treated-with-continuous-renal-replacement-therapy
#10
Akihide Nakamura, Kei Suzuki, Hiroshi Imai, Naoyuki Katayama
Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication. We report a case of MALA in a man aged 71 years who was treated with continuous renal replacement therapy (CRRT). The patient was brought to the hospital for prolonged and gradual worsening gastrointestinal symptoms. Although he received intravenous treatment, he developed catecholamine-resistant shock, and blood gas analysis revealed lactic acidosis. Bicarbonate and antibiotics for possible sepsis were initiated, but with no clear benefit...
February 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28185288/metformin-effects-on-head-and-neck-squamous-carcinoma-microenvironment-window-of-opportunity-trial
#11
Joseph Curry, Jennifer Johnson, Patrick Tassone, Marina Domingo Vidal, Diana Whitaker Menezes, John Sprandio, Mehri Mollaee, Paolo Cotzia, Ruth Birbe, Zhao Lin, Kurren Gill, Elizabeth Duddy, Tingting Zhan, Benjamin Leiby, Michelle Reyzer, David Cognetti, Adam Luginbuhl, Madalina Tuluc, Ubaldo Martinez-Outschoorn
OBJECTIVE: The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors. STUDY DESIGN: Window of opportunity trial of metformin between diagnostic biopsy and resection...
February 10, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28158227/beneficial-effects-of-metformin-on-energy-metabolism-and-visceral-fat-volume-through-a-possible-mechanism-of-fatty-acid-oxidation-in-human-subjects-and-rats
#12
Ichiro Tokubuchi, Yuji Tajiri, Shimpei Iwata, Kento Hara, Nobuhiko Wada, Toshihiko Hashinaga, Hitomi Nakayama, Hiroharu Mifune, Kentaro Yamada
OBJECTIVE: Metformin is known to have a beneficial effect on body weight and body composition, although the precise mechanism has not been elucidated yet. The aim of this study is to investigate the effects of metformin on energy metabolism and anthropometric factors in both human subjects and rats. METHODS: In human studies, metformin (1500mg/day) was administered to 23 healthy subjects and 18 patients with type 2 diabetes for 2 weeks. Metabolic parameters and energy metabolism were measured during a meal tolerance test in the morning before and after the treatment of metformin...
2017: PloS One
https://www.readbyqxmd.com/read/28139970/hemodialysis-refractory-metformin-associated-lactate-acidosis-with-hypoglycemia-hypothermia-and-bradycardia-in-a-diabetic-patient-with-belated-diagnosis-and-chronic-kidney-disease%C3%A2
#13
Lada Zibar, Karin Zibar
Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus. Metformin-associated lactate acidosis (MALA) is a well-known, life-threatening, but rare side effect of metformin therapy. Chronic kidney disease (CKD) patients have a much greater risk of MALA. We report the case of a severe refractory MALA despite hemodialysis (HD) treatment, associated with hypoglycemia, hypothermia, and bradycardia in a neglected and thus untimely-recognized CKD patient with type 2 diabetes mellitus...
April 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28134407/-metformin-associated-lactic-acidosis-and-acute-kidney-injury
#14
Paolo Greco, Giuseppe Regolisti, Riccardo Antoniotti, Caterina Maccari, Elisabetta Parenti, Silvia Corrado, Enrico Fiaccadori
Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because of its efficacy, general tolerability and low cost. Recent guidelines have extended the use of metformin to patients with Chronic Kidney Disease (CKD) up to stage III. However, in the recent literature, cases of MALA (metformin-associated lactic acidosis) are increasingly reported. MALA is the most dangerous side effect of the drug, with an incidence rate of 2-9 cases per 100000 person-years of exposure. We report on two patients with accidental metformin overdose, severe lactic acidosis and acute kidney injury...
November 2016: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28120561/association-between-metformin-use-and-risk-of-lactic-acidosis-or-elevated-lactate-concentration-in-type-2-diabetes
#15
Eun Young Lee, Sena Hwang, Yong Ho Lee, Seo Hee Lee, Young Mi Lee, Hua Pyong Kang, Eugene Han, Woonhyoung Lee, Byung Wan Lee, Eun Seok Kang, Bong Soo Cha, Hyun Chul Lee
PURPOSE: Metformin can reduce diabetes-related complications and mortality. However, its use is limited because of potential lactic acidosis-associated adverse effects, particularly in renal impairment patients. We aimed to investigate the association of metformin use with lactic acidosis and hyperlactatemia in patients with type 2 diabetes. MATERIALS AND METHODS: This was a cross-sectional study from a tertiary university-affiliated medical center. A total of 1954 type 2 diabetes patients were recruited in 2007-2011, and stratified according to the estimated glomerular filtration rate of 60 mL/min/1...
March 2017: Yonsei Medical Journal
https://www.readbyqxmd.com/read/28052008/targeting-p-glycoprotein-function-p53-and-energy-metabolism-combination-of-metformin-and-2-deoxyglucose-reverses-the-multidrug-resistance-of-mcf-7-dox-cells-to-doxorubicin
#16
Chaojun Xue, Changyuan Wang, Yaoting Sun, Qiang Meng, Zhihao Liu, Xiaokui Huo, Pengyuan Sun, Huijun Sun, Xiaodong Ma, Xiaochi Ma, Jinyong Peng, Kexin Liu
Multidrug resistance(MDR) is a major obstacle to efficiency of breast cancer chemotherapy. We investigated whether combination of metformin and 2-deoxyglucose reverses MDR of MCF-7/Dox cells and tried to elucidate the possible mechanisms. The combination of metformin and 2-deoxyglucose selectively enhanced cytotoxicity of doxorubicin against MCF-7/Dox cells. Combination of the two drugs resumed p53 function via inhibiting overexpression of murine doubleminute 2(MDM2) and murine doubleminute 4(MDM4) leading to G2/M arrest and apoptosis in MCF-7/Dox cells...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27981898/the-role-of-carbonic-anhydrase-in-hepatic-glucose-production
#17
Ibrahim Salihu Ismail
Considerable efforts are being made daily to discover novel therapeutic targets to better understand the mechanism for designing drugs in treating diabetes. Inhibition of hepatic gluconeogenesis by metformin remains the first line of oral therapy for managing type 2 diabetes. The link between rise in blood lactate level and reduction of hepatic glucose production with metformin usage remains to be determined. Carbonic anhydrase is proposed to be the link connecting blood lactate accumulation and inhibition of hepatic gluconeogenesis and thus could serve as a new therapeutic target for reducing hepatic glucose production...
December 14, 2016: Current Diabetes Reviews
https://www.readbyqxmd.com/read/27904044/investigation-of-risk-factors-affecting-lactate-levels-in-japanese-patients-treated-with-metformin
#18
Shota Yokoyama, Hideyuki Tsuji, Sachiko Hiraoka, Masayuki Nishihara
Metformin is a biguanaide antidiabetic drug used worldwide, and its effectiveness and benefits have already been established. However, the safety of high doses of metformin in Japanese patients, especially in elderly patients with a decreased renal function, remains unclear. Among the side effects of metformin, lactate acidosis is the most problematic due to a high mortality rate. Therefore, we assessed plasma lactate levels in metformin-treated patients to identify independent risk factors for hyperlactemia...
2016: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/27889750/metformin-protects-neurons-against-oxygen-glucose-deprivation-reoxygenation-induced-injury-by-down-regulating-mad2b
#19
Xianfang Meng, Guangpin Chu, Zhihua Yang, Ping Qiu, Yue Hu, Xiaohe Chen, Wenpeng Peng, Chen Ye, Fang-Fang He, Chun Zhang
BACKGROUND/AIMS: Metformin, the common medication for type II diabetes, has protective effects on cerebral ischemia. However, the molecular mechanisms are far from clear. Mitotic arrest deficient 2-like protein 2 (MAD2B), an inhibitor of the anaphase-promoting complex (APC), is widely expressed in hippocampal and cortical neurons and plays an important role in mediating high glucose-induced neurotoxicity. The present study investigated whether metformin modifies the expression of MAD2B and to exert its neuroprotective effects in primary cultured cortical neurons during oxygen-glucose deprivation/reoxygenation (OGD/R), a widely used in vitro model of ischemia/reperfusion...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27861334/lactic-acidosis-and-the-relationship-with-metformin-usage-case-reports
#20
Weiyi Huang, Ronald L Castelino, Gregory M Peterson
AIMS: The principal objective of this study was to retrospectively review a series of cases of lactic acidosis (LA) in patients with type 2 diabetes mellitus (T2DM) and examine the relationship with the use of metformin. More generally, the study enabled an investigation of the profiles of patients diagnosed with LA and clinical variables associated with in-hospital mortality. METHODS: All patients admitted to the Royal Hobart Hospital in Tasmania with LA (lactate >5...
November 2016: Medicine (Baltimore)
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